Thursday, 28 February 2019

EQE Paper A 2019 - Cell culturing device

Paper A of 2019 concerned a device for culturing cells. Different from the prior art, a gas-permeable membrane is used to form a cell culture chamber, which improves the exchange of gases and therefore increases cell growth.

Several issues were tested in this paper.

The paper provided two different ways of accessing the cell culture chamber: by way of an aperture in the frame or by temporarily opening and resealing one of the membranes. These two options should be covered by the main claim. The paper suggested the genus 'opening' to cover these two possibilities.

For some of the features it was mentioned that they were essential, and thus should be included in the claim. For example, that the membranes are liquid-impermeable is essential for all embodiments, and should thus be included in claim 1. Other features are only essential for some embodiments. For example, in the embodiment according to the figures, with an aperture through the frame, it is essential that the aperture is leak-proof.

The paper provided lots of features that could potentially be claimed. At the same time the client indicated that he did not want to pay additional claim fees, so that the candidates had to prioritize which features to claim and which not to. Some of these features were known from the prior art or obviously solve a problem. Such dependent claims will not provide a suitable fall-back position and should be omitted. For example, no claim should be formulated for: an optically transparent membrane, or adhesion coating; these are known features that bring their known advantages. Likewise, we think no claim should be formulated for the gas-permeability ranges for O2 and CO2. The ranges as stated are anticipated in the prior art, and no hint is provided how these ranges could be limited in an inventive manner. Also no claim seem needed for a rectangular frame. This is an obvious adaptation of the frame.

The gasket is a bit harder to decide. On the one hand it is a 'type of mechanical' seal, and thus presumably known in the art. On the other hand, the cited art does not mention gaskets, so probably their use in the field of cell culture chambers is not known. Furthermore, the gaskets provide a clear advantage. Accordingly, the use of gaskets in the field of cell chambers seems a good fall-back.

Another difficulty concerned the method of culturing cells. One could argue that all steps of such a method are known except for the use of the inventive cell culturing device. Accordingly, the method does not seem to protect anything that isn't already protected by the device claims. On the other hand, the method does cover the main use of the cell culture device and so may provide a fall-back position. The paper suggests that the cell culture device can be tilted, but does not explain why one would want to do so. If the intention is that tilting is beneficial for cell growth, then a method claim may be formulated that includes a tilting or shaking step. Probably, it is the intention however that this is an advantage of the full-filling of the chamber, and so no claim is required.

We find it conceivable that one would omit the cell-culturing methods and instead rely on  the protection of the device claims. If one were to go that way, one may need to include a device claim in which the cell chamber is completely filled with cell suspension.

 Below are the claim according to our solution:

1. A device for culturing cells comprising
-          a frame (1),
-          a first and second gas-permeable and liquid-impermeable membrane (2a, 2b), wherein the membranes are attached to the frame by means of a leak-proof seal forming a  cell culture chamber (4) between the opposing first and second membranes and the frame, and
-          at least one leak-proof resealable opening (3a, 3b) that allows substances to be introduced into or withdrawn from the culture chamber.

2. A device according to claim 1, wherein at least one leak-proof resealable opening (3a, 3b) is a leak-proof resealable aperture (3a, 3b) provided through the frame (1).

3 A device according to claim 2, wherein the at least one leak-proof resealable aperture comprises a gasket.

4. A device according to claim 3 wherein the gasket comprises an elastomeric material.

5. A device according to claim 4 wherein the gasket further comprises an antimicrobial agent integrated in the elastomeric material.

6. A device according to any one of claims 2 to 5, wherein the aperture has a diameter of 1 to 2 mm.

7. A device according to any one of claims 2 to 6, wherein the frame comprises two or more leak-proof resealable apertures (3a, 3b) allowing a user to introduce a substance into the cell culture chamber via one of the apertures while another substance is removed via another one of the apertures.

8. A device according to any one of the preceding claims, wherein at least one membrane of the first and second membrane is a leak-proof resealable membrane forming the at least one leak-proof resealable opening, wherein the at least one membrane is attached to the frame with a pressure-sensitive adhesive.

9. A device according to any one of the preceding claims, wherein an average distance of between 1 mm to 5 mm is provided between the first and second membranes.

10. A rack for holding a cell culture device according to any one of the preceding claims in an incubator, the rack being configured to provide a space between the first and second membrane and the incubator to allow air to circulate.

11. A method of culturing cells, the method comprising
(a)  suspending the cells to be cultured in an appropriate amount of cell culture medium to form a cell suspension;
(b)  introducing the cell suspension into the cell chamber of a cell culture device according to any one of the preceding claims
(c)  incubating the cell culture device containing the cell suspension in conditions allowing cell growth.

12. A method of culturing cells according to claim 11 comprising filling the cell culture chamber completely with a cell suspension such that there is no head space containing air.

13. A method of manufacturing a device according to any one of claims 1 to 9, comprising
-          providing a frame (1),
-          providing a first and second gas-permeable and liquid-impermeable membrane (2a, 2b),
-          attaching the membranes to the frame to establish a leak-proof seal between the membranes and the frame, so that the membranes oppose each other and a cell culture chamber (4) is formed between the opposing membranes and the frame, and
-          providing at least one leak-proof resealable opening (3a, 3b) that allows substances to be introduced into or withdrawn from the culture chamber.

14. A method of manufacturing a device according to claim 13 comprising establishing the leak-proof seal using a pressure-sensitive adhesive.

15. A method of manufacturing a device according to claim 14 comprising establishing the leak-proof seal by ultrasonic welding.